Individual tumor suppression strategy using cancer antigen peptides in oral cancers

使用癌症抗原肽治疗口腔癌的个体化肿瘤抑制策略

• 批准号: 21792045
• 负责人: YAMATE Chizu
• 金额: $ 1.41万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21792045/
• 关键词: 口腔癌; 癌特異免疫; ペプチド; 癌ワクチン療法

Among 31 types of cancer antigen peptide, which were identified by the Department of Immunology, Kurume University, we investigated the possibility of p56^<lck> and SART-3 cancer antigen peptides becoming target molecules of specific cancer vaccine therapy for patients with oral squamous cell carcinoma. The subjects were primary cases of oral squamous cell carcinoma, which were treated in the Dental and Oral Medical Center, Kurume University School of Medicine. We immunohistochemically evaluated the expression of p56^<lck> antigen, using anti-rabbit monoclonal antibodies, and the positive rate was 13/27 (48%). Furthermore, using the RT-PCR method, the expression of p56^<lck> and SART-3 molecules in the cell lines of oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4, Ca9-22, KUMA-1, SAS) and oral cancer resection tissue was confirmed. On the other hand, using the Western blotting method, the expression of SART-3 antigen in the nuclear and cytosolic fractions was evaluated, and the expression rate was 100% in each cell line. In the oral cancer resection tissue, the expression rate was 19/31 (61%)in the nuclear fraction and 12/31 (39%)in the cytosolic fraction. Furthermore, measuring the amount of IFN-γ production using the ELISA method, we evaluated the HLA-24-restricted induction of CTL by p56^<lck> and SART-3 peptides, and peptide-specific induction of CTL was confirmed from the peripheral blood in patients with oral squamous cell carcinoma. Considering these results and that approximately 60% of Japanese people have HLA-A24, there is a possibility that p56^<lck> and SART-3 molecules can be used as target molecules in tailor-made peptide vaccine therapy.

在库鲁姆大学免疫学系鉴定的31种肿瘤抗原肽中，我们探讨了p56^<lck>和SART-3肿瘤抗原肽成为口腔鳞状细胞癌特异性肿瘤疫苗治疗靶分子的可能性。研究对象为在库鲁姆大学医学院口腔医学中心接受治疗的口腔鳞状细胞癌原发病例。采用抗兔单克隆抗体，免疫组化检测p56^<lck>抗原的表达，阳性率为13/27（48%）。利用RT-PCR方法，证实p56^<lck>和SART-3分子在口腔鳞状细胞癌细胞系（HSC-2、HSC-3、HSC-4、Ca9-22、KUMA-1、SAS）和口腔癌切除组织中的表达。另一方面，采用Western blotting法检测SART-3抗原在细胞核和细胞质部分的表达，各细胞系的表达率均为100%。在口腔癌切除组织中，细胞核部分表达率为19/31(61%)，细胞质部分表达率为12/31（39%）。此外，利用ELISA法测定IFN-γ的生成量，我们评估了p56^<lck>和SART-3肽对hla -24限制性CTL的诱导作用，并证实了口腔鳞状细胞癌患者外周血中对CTL的肽特异性诱导作用。考虑到这些结果以及大约60%的日本人有HLA-A24， p56^<lck>和SART-3分子有可能被用作定制肽疫苗治疗的靶分子。